Infecting mosquitos with bacteria could block malaria

Getting Wolbachia bacteria to grow in mosquitos may help human health.

Mosquito bites kill an estimated 1-2 million people every year. It is not the mosquitoes’ fault, though—it's the pathogens they transmit that are lethal, not the bites themselves. Nets and insecticides can help, but they can also be costly, logistically difficult to distribute, and not particularly green. So alternative strategies to prevent disease transmission are needed.

Wolbachia are bacteria that reside in insect cells and have a very complicated relationship with their hosts. They can render mosquitoes resistant to certain pathogens, and they can reduce mosquitoes' lifespans, which is significant because it is often the older mosquitoes that transmit the pathogens that make us sick. Wolbachia infect up to 76 percent of the 2-5 million insect species on Earth—but not, of course, the mosquito species that carry dengue fever or malaria. That would be far too convenient.

So researchers have been trying to infect disease-carrying mosquitoes with Wolbachia in the lab and then let these infected mosquitoes out into the wild to mate with and infect disease-carrying strains in order to reduce disease transmission. This has in fact already happened in northeastern Australia, where researchers spent four years maintaining Wolbachia in mosquito cells in the lab before letting infected mosquitoes loose in January 2011 to infect wild Aedes aegypti, the mosquitoes that transmit dengue fever. The trial is going so well that it is being repeated in Vietnam.

But the mosquitoes that transmit malaria in the Middle East and South Asia, Anopheles stephensi, have resisted attempts to infect them with Wolbachia for the past twenty years or so. Finally, researchers have succeeded in not only infecting A. stephensi with Wolbachia but in maintaining the infection over 34 generations.

In each generation, each infected female passed the bacteria on to 100 percent of her offspring. Infected mosquitoes had an almost four-fold reduction in Plasmodium falciparum, one of the parasites that causes malaria. When the researchers seeded cages of uninfected mosquitoes with only five percent infected females, 100 percent of the mosquitoes were infected within eight generations. However, they also had to put in twice as many infected males as there were uninfected ones to "suppress the effective mating" of uninfected females, which could prove problematic if this strategy were to be implemented on a large scale in the wild.

There is no evidence that Wolbachia is transferred to humans via mosquito bites or to mosquito predators like geckos and spiders. The incidence of mosquito-borne diseases is increasing due to the ease of air travel and the rapid urbanization of developing countries; infecting mosquitoes to make them resistant to pathogens might be a relatively cheap and green addition to the public health measures currently used to deal with them.

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People that worry about the consequences of using Wolbachia : 76 % of insect species already have it, it's been everywhere for millions of years already. It's not really a parasite, it's on its way to become a symbiont like the chloroplast and the mitochondria.

Interesting if they can get the malaria variant out into the wild but they'll likely need a better way to handle the uninfected other than just mass spamming infected males to overwhelm the current uninfected females.

Does the article mention how much infected they needed to release in Australia to get the results?

This is really nice news, and nice progress against a devastating disease. By forced passage of the bacteria, the researchers are, I guess, using a principle to redesign the bacteria which we are all worried about in the context of avian influenza viruses jumping species. So it's an upside to a generally worrying biological phenomenon. Good stuff.Nevertheless, we should be careful not to underestimate the way in which both mosquitoes and P. falciparum can change in response to the changes we impose upon them. A friend of mine works on insecticide resistance in mosquitoes and maintains that one of the best ways to combat malaria has been to use bed nets, particularly ones coated with fly killer. Mosquitoes transmit the parasites when they feed in the dark of the evening/night hence why bed nets can be effective. However following the increased use of bed nets, the mosquito population has responded by being composed of an increasing number which feed earlier in the evening, before people are safely protected by their nets.

I remember reading an article a number of years ago about a virus that could be engineered to kill mosquitos after 10 days--before the malaria parasite is able to infect humans. The virus wouldn't be selected out because it does not affect mosquitos' ability to reproduce.

I guess that research was a dead end? I'm pretty sure I read it on this site, but arstechnica doesn't have any articles from before 2012 that I can find using search.

human attempts to eradicate certain insect-borne diseases by introducing creative pathogens into a new insect population is probably number 5 on my list of things that may accidentally wipe out the human race. http://en.wikipedia.org/wiki/Mimic_(film)

*Edit: Apparently this came off as flippant, but I'm actually quite serious. Sure, for all intents and purposes, introducing a bacteria that already lives inside most mosquito species into a different mosquito species isn't ostensibly much of a high-risk activity. but, IMHO, it merits a discussion of the same kinds of considerations implicated in trans-species pathogen introduction schemes with more readily identifiable dangers.

The best solution to me, as a non-specialist, would be to find a solution preventing mosquitoes from carrying malaria and at the same time improving their chances of breeding. That could naturally select those without malaria, giving rise to more annoying but much less dangerous buggers.

This is Nevertheless, we should be careful not to underestimate the way in which both mosquitoes and P. falciparum can change in response to the changes we impose upon them.

I agree this is a concern but it's useful to keep in mind that unlike static insecticide treatments, Wolbachia have the ability to evolve and adapt to the adaptations of the mosquitoes.

Nice idea Dan, and I hope that you're right*. Tho' I get the feeling that we're hammering an evolutionary square peg into a round hole on this one, and that the Wolbachia may become less virulent over time. Heck, I'm going to read the Science article...

*Edit - on thinking a bit more about this, perhaps if the forced passage through A. stephensi has overcome a roadblock for Wolbachia which now finds itself in a new evolutionary niche into which it can expand, and, as you say evolve and adapt

human attempts to eradicate certain insect-borne diseases by introducing creative pathogens into a new insect population is probably number 5 on my list of things that may accidentally wipe out the human race. http://en.wikipedia.org/wiki/Mimic_(film)

People whose science knowledge comes primarily from movie pseudoscience and TV quackery are on my top list of things that may accidentally wipe out the human race.

So by the time I hopefully get to return to Africa, I will have to receive a Wolbachia vaccine or take Anti-Wolbacchia. Hopefully this won't be in addition to anti-malarial pills. Those are unpleasant.

People that worry about the consequences of using Wolbachia : 76 % of insect species already have it, it's been everywhere for millions of years already. It's not really a parasite, it's on its way to become a symbiont like the chloroplast and the mitochondria.

So by the time I hopefully get to return to Africa, I will have to receive a Wolbachia vaccine or take Anti-Wolbacchia. Hopefully this won't be in addition to anti-malarial pills. Those are unpleasant.

Considering it does not transmit to humans you won't need any kind of vaccine or treatment with the Wolbacchia bacteria.

human attempts to eradicate certain insect-borne diseases by introducing creative pathogens into a new insect population is probably number 5 on my list of things that may accidentally wipe out the human race. http://en.wikipedia.org/wiki/Mimic_(film)

People whose science knowledge comes primarily from movie pseudoscience and TV quackery are on my top list of things that may accidentally wipe out the human race.

human attempts to eradicate certain insect-borne diseases by introducing creative pathogens into a new insect population is probably number 5 on my list of things that may accidentally wipe out the human race. http://en.wikipedia.org/wiki/Mimic_(film)

People whose science knowledge comes primarily from movie pseudoscience and TV quackery are on my top list of things that may accidentally wipe out the human race.

No need to get dickish about it.

Posting guidelines:

Quote:

Ad hominem and personal attacks are not permitted.

You cited a movie in support of your point, and your description of your point, in the context of the article under discussion, indicates a lack of understanding of the mechanisms by which pathogens infect hosts.* However, the reply did not call you names, but merely criticize people whose logic is similar to your own. Thus, it would appear that . . . Never mind. Unlike some around here, I try to avoid trolling.

*Humans have been (successfully) competing with partially or totally human-adapted viral and bacterial pathogens for the entirety of their existence. The likelihood of an insect-infecting bacteria that has been endemic in insect populations for an extended period suddenly altering to be able to render the human species extinct before a combination of evolutionary processes and scientific research halted the process is, to say the least, extraordinarily unlikely.

This is Nevertheless, we should be careful not to underestimate the way in which both mosquitoes and P. falciparum can change in response to the changes we impose upon them.

I agree this is a concern but it's useful to keep in mind that unlike static insecticide treatments, Wolbachia have the ability to evolve and adapt to the adaptations of the mosquitoes.

Nice idea Dan, and I hope that you're right*. Tho' I get the feeling that we're hammering an evolutionary square peg into a round hole on this one, and that the Wolbachia may become less virulent over time. Heck, I'm going to read the Science article...

*Edit - on thinking a bit more about this, perhaps if the forced passage through A. stephensi has overcome a roadblock for Wolbachia which now finds itself in a new evolutionary niche into which it can expand, and, as you say evolve and adapt

The Wolbachia in his case is presumably not virulent towards the host, but towards the host's rival parasite, which it presumably does not infect, but simply competes with. So any evolving done would have to be by the plasmodium, to deal with the new environment which now includes Wolbachia. As the Wolbachia are passed through the germ line they are difficult for later infections to dislodge.

Isn't there a virus that preys on the malarial parasite? If not could we engineer one? If so could we make it more virulent where it makes the parasite more susceptible to our immune system.

The malaria parasite spends like 99% of its life in a human cell of some sort or an insect cell of some sort. Do you want to create a latent viral infection in the human or one in the insect so that there's actual viruses around ready to infect malaria parasites ? How easy is it to create a virus that can infect (but is not killed off entirely by) insects as well as the malaria parasite ?

It would be better to use something like the bacteria that naturally infects insects for this.... seems safer than convincing people to infect themselves with bacteria or viruses that the body shouldn't completely kill off. Oh, and that's what they're doing.

For reference, I'm not sure there's really any viruses that target the malaria parasite and only the malaria parasite. In the more common red blood cell stage the parasite is inside a (mostly inactive) red blood cell and has a "bubble" of parasite and human membranes around it. Not impossible, but a number of barriers to cross before you hit parasite.

Wolbachia is certainly an interesting bacterium, and there is a certain irony in this news. That is that malaria is not the only disease which mosquitoes spread. One other disease spread by mosquitoes is filariasis (microscopic worms which infest your lymphatics and blood). Recent research also discovered that adult filarial worms could be killed by taking an antibiotic which would KILL Wolbachia in the worms' guts, apparently killing the worm because it has become dependent on Woknachia to digest its food and therefore essential for the worms' survival.

"In the process of analyzing the Brugia malayi genome as part of the Filarial Genome Project it was observed that the worms contained Wolbachia, obligate intracellular alpha-proteobacteria which are present in all human and many animal filarial parasites. Related organisms are present in up to 70% of arthropod species. In arthropods, the Wolbachia have been shown to cause reproductive abnormalities in their hosts, leading to aberrant sex ratios, reciprocal cross sterility (cytoplasmic incompatablities), parthenogenesis and feminization of genetic males."